The impact of time, polycystic ovarian syndrome and pregnancy in Idiopathic Intracranial Hypertension

Thaller, Mark Joseph ORCID: 0000-0001-7772-2157 (2024). The impact of time, polycystic ovarian syndrome and pregnancy in Idiopathic Intracranial Hypertension. University of Birmingham. Ph.D.

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Abstract

Background
Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure (ICP) predominately affecting women of reproductive age with obesity. Its incidence is rising in line with obesity rates. There are unmet needs to evaluate the longitudinal visual and headache outcomes, identify prognostic factors, and assess the impact of comorbid conditions such as polycystic ovarian syndrome (PCOS) and the event of pregnancy. In addition, this work was undertaken during the coronavirus pandemic which significantly impacted hospital services and naturally forms the introductory chapter to this COVID-era thesis. This thesis was based on the prospective cohort study, IIH: Life, from Birmingham, and maternal health data from the UK Hospital Episodes Statistics dataset.
There was a clear need for a large prospective cohort study to evaluate visual and headache outcomes over time and help identify any prognostic markers. The benefit of this research was to improve the management of IIH patients by identifying the key modifiable risk factors that affect prognosis.
The commonest endocrinopathy in women of reproductive age is PCOS, which is known to affect pregnancy and fertility and prior literature indicates in more prevalent in women with IIH. Therefore, it is important to evaluate the comorbidity of PCOS and whether it impacts outcomes. Fertility and pregnancy may be impacted by shared mechanisms with PCOS including obesity, metabolic profiles and hyperandrogenism, or through alternative pathways. However, the impact of a diagnosis of IIH has not yet been established and warrants further research.
Pregnancy has the potential to impact IIH longitudinal outcomes due to the associated gestational weight gain, hormonal changes, and the limited treatment options. However, the outcomes have been under investigated with only two published studies, and therefore the guidance has often been to avoid pregnancy and avoid active labour. These themes form an important thread within this thesis.
This thesis aimed to assess the impact of time, PCOS, and pregnancy in IIH in order to improve the management of IIH in women of childbearing age.

Findings
Following the first COVID-19 lockdown, a significant impact on the incidence and management of IIH was observed. Amongst the patients seen in our emergency papilloedema clinic, approximately one-third presented with new onset IIH. Additionally, in individuals with previously diagnosed IIH, a majority (58%) experienced weight gain during the lockdown period, with an average increase of 6.2 kg (standard deviation (SD) 4.6). Importantly, this weight gain was found to be statistically associated with a significant worsening of papilloedema (p=0.013). Furthermore, the emergency CSF diversion surgery (shunting) rate rose 4.7-fold compared to the same period in 2019. Most worryingly, 13% of all IIH patients seen in those 2.5 months had surgical interventions with 21% of the new onset IIH group requiring surgery.
The longitudinal prospective cohort study, IIH: Life, included 490 patients with a confirmed IIH diagnosis. The cohort predominantly consisted of females (98%) with a mean body mass index (BMI) of 38 kg/m2. The study revealed that patients with the thickest ocular coherence tomography (OCT) retinal nerve fibre layer (≥400 µm) exhibited the worst visual outcomes. We noted a delayed decline in the visual field and OCT ganglion cell layer after 12 months. Within the medically managed cohort (n = 426), we found that disease duration and change in BMI had the greatest influence on visual outcomes. There was a substantial burden of headache observed, with a daily headache at presentation and a prior migraine history influencing the long-term headache prognosis.
Atypical presentations of IIH, characterized by asymptomatic or with a normal BMI at diagnosis, were uncommon (10%) and rare (3.7%) respectively. In the asymptomatic cohort most patients developed symptoms over the course of their follow up, and the trajectories were similar regardless of the initial presence or absence of symptoms. Although a normal BMI at the baseline visit was associated with worse visual field function, papilloedema measurements were analogous, and long-term outcomes did not significantly differ between the groups.
Comorbid PCOS in IIH was common (20%, 78/398) in our cohort based on the Rotterdam criteria. The presence of PCOS was associated with a 3.2-fold increased risk of self-reported fertility problems and 4.4-fold for requiring medical intervention for pregnancy. However, it was worth noting that comorbid PCOS did not adversely impact long-term vision or headache outcomes in people living with IIH.
Pregnancy in individuals with IIH presented unique challenges and considerations. An IIH diagnosis was associated with an increased risk of pre-eclampsia (5.3-fold) and gestational diabetes (2.7-fold) compared to the general population. Pre-eclampsia was also increased compared to a PCOS population (3-fold), but not gestational diabetes. Furthermore, reduced birth rates and increased caesarean section rates were also observed. In people with IIH who subsequently became pregnant, pregnancy did not adversely affect visual or headache outcomes and was akin to those with IIH that had never had a pregnancy. IIH diagnosed in pregnancy was rare (2%) but associated with greater papilloedema. However, visual field and acuity measurements were comparable to those with established IIH who became pregnant.

Conclusions
People with IIH were adversely affected by the first COVID-19 national lockdown. Overall IIH has been found to be negatively influenced by papilloedema severity, daily headache at presentation and a personal migraine history, but positively improved by weight loss. Whilst it was found there was a 20% comorbid PCOS prevalence and self-reported fertility problems in this IIH cohort; PCOS was not associated with longer-term adverse outcomes. IIH was also shown to impact fertility, preeclampsia risk, gestational diabetes risk and caesarean section rates. IIH outcomes were impacted when IIH was diagnosed in pregnancy but not in those with established IIH who had a subsequent pregnancy. This body of work has furthered the literature with these new findings of adverse maternal health associations, outlined the spectrum of IIH, and highlighted the neutral influence of pregnancy for the majority of women living with IIH.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):